Dataset Information

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

ABSTRACT: AIMS:Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CDCA5 expression in our well-characterized UC cohort. METHODS AND RESULTS:Quantigene assay was used to detect CDCA5 transcript levels in 36 UTUCs and 30 UBUCs. We used immunohistochemistry evaluated by H-scores to determine CDCA5 protein expression in 295 UBUCs and 340 UTUCs, respectively. CDCA5 expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). For both groups of UCs, increments of CDCA5 transcript levels were associated with higher pT status, CDCA5 protein overexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses. CDCA5 overexpression was predictive for worse DSS and MeFS in univariate and multivariate analysis. CONCLUSIONS:CDCA5 overexpression is associated with advanced clinical features of UC, suggesting its potential value as a prognostic biomarker and a novel therapeutic target.

SUBMITTER: Chang IW

PROVIDER: S-EPMC4455346 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

Chang I-Wei IW Lin Victor Chia-Hsiang VC He Hong-Lin HL Hsu Chao-Tien CT Li Ching-Chia CC Wu Wen-Jeng WJ Huang Chun-Nung CN Wu Ting-Feng TF Li Chien-Feng CF

American journal of translational research 20150415 4

<h4>Aims</h4>Urothelial carcinoma (UC) is the most common tumor involving upper urinary tract (UTUC) and urinary bladder (UBUC) whose molecular survival determinants remains obscured. By computerizing a public transcriptomic database of UBUCs (GSE32894), we identified cell division cycle associated 5 (CDCA5) as the most significantly upregulated gene among those associated with G1-S transition of the mitotic cell cycle (GO:0000082). We therefore analyzed the clinicoptaological significance of CD ...[more]

PMID: 26064439

Similar Datasets

Project description:BACKGROUND AND AIMS:Oncogenesis is a multistep process, resulting from the accumulations of multiple mutations. Of these mutations, self-sufficiency in growth signals, i.e., disruption of cell growth regulation, is the first episode. Nonetheless, the genes associated with cell growth dysregulation have seldom been systematically evaluated in either urothelial carcinomas of upper urinary tract (UTUC) or urothelial carcinomas of urinary baldder (UBUC). By data mining a published transcriptomic dataset of UBUCs (GSE31684), we identified the NDN gene as one of the most significant of those associated with the regulation of cell growth and found this gene is associated with advanced tumor status and metastatic disease (GO:0001558). Accordingly, we analyzed NDN transcript and protein expression with their clinicopathological significance. MATERIALS AND METHODS:We used real time RT-PCR to detect NDN transcript levels in 27 UTUCs and 27 UBUCs, respectively. Immunohistochemical study was performed to determine NDN protein (a.k.a. Necdin) expression evaluated by H-score method in 340 UTUCs and 295 UBUCs. NDN expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). RESULTS:NDN transcriptional level was significantly higher in UCs of both sites with stepwise more advanced pT statuses. Through immunohistochemistry, we found NDN protein expression was significantly associated with adverse clinicopathological parameters, e.g., advanced pT status, nodal metastasis, high grade histological patterns, and frequent mitotses (all P<0.05). In univariate analysis, NDN overexpression not only predicted worse DSS and MeFS in both the UTUC and UBUC groups, it also served as an independent prognostic factor for DSS and MeFS in multivariate analysis (all P<0.05). CONCLUSIONS:NDN may play an important role in tumor progression in UC and could serve as a prognostic biomarker and a potential novel therapeutic target in UC.

Project description:Background: The TP53 tumor suppressor gene plays a crucial role in the carcinogenesis of many malignancies, including urothelial carcinoma (UC). Overexpression of p53 is associated with poor prognosis in UC. Recently, RING finger protein 128 (RNF128) was shown to be involved in p53-induced apoptosis, forming a negative feedback loop. However, the significance of RNF128 in patients with UC remains unknown. In this study, our aim was to evaluate the expression of RNF128 in UC and to assess its predictive and prognostic value in a well-established cohort. Methods: Through data mining from a published transcriptome (GSE31684), RNF128 was identified as the most differentially expressed gene in UC among those associated with negative regulation of the cytokine biosynthetic process (GO:0042036). Its immunoexpression was further evaluated using the H-scores of 340 patients with upper urinary tract UC (UTUC) and 295 with urinary bladder UC (UBUC). The scores were correlated with clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MeFS). We also used Western blot analysis to evaluate RNF128 protein expression in human urothelial cell (HUC) lines. Results: Downregulation of RNF128 expression was significantly associated with advanced pT stage (p<0.001), high histological grade (UTUC, p<0.001; UBUC, p=0.035), nodal metastasis (UTUC, p<0.001; UBUC, p=0.001), vascular invasion (UTUC, p<0.001; UBUC, p=0.008) and high mitotic rate (UTUC, p=0.003; UBUC, p=0.023). Low expression of RNF128 was an adverse prognosticator for DSS (UTUC, p<0.0001; UBUC, p<0.0001) and MeFS (UTUC, p<0.0001; UBUC, p=0.0002). Moreover, low expression was predictive of poor DSS (UTUC, p=0.006; UBUC, p=0.003) and MeFS (UTUC, p=0.009; UBUC, p=0.036) in multivariate comparisons. Western blot analysis showed that the RNF128 protein was downregulated in invasive urothelial cancer cell lines. Conclusion: Our findings showed that downregulation of RNF128 was correlated with cancer invasiveness and metastasis as well as reduced survival in patients with UTUC and UBUC, identifying RNF128 as a prognostic factor in UC.

Dataset Information

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

Publications

CDCA5 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure